The activation of the coagulation system culminating in the conversion of fibrinogen to fibrin is a commonly evoked pathogenetic event in thrombotic diseases as well as diseases associated with blood vessel injury, or an inflammatory reaction. The dissolution of fibrin deposits either within the vascular compartment or outside blood vessels, is cenral to the reestablishment of vascular integrity and normal hemostasis as well as to the resolution of the primary pathogenetic events. Although the plasminogen system has been considered to be the major pathway for fibrinolysis, leukocytes contain an alternative fibrinolytic system which may provide an important physiologic alternative for fibrinolysis. We propose to explore and elucidate the molecular and physiologic parameters of this alternative fibrinolytic system. The molecular characteristic of the enzymes involved and the cleavage fragments generated will be examined and contrasted with the plasminogen system. The biologic activities of the cleavage fragments generated by leukocyte proteases will be considered in terms of their role as effectors within the entire coagulation system and also as initiators and mediators of the inflammatory response. The release of physiologically active fibrinolytic proteases from leukocytes and the physiologic control of the release reaction will be examined. It is anticipated that these approaches should provide greater insight into the role of the leukocyte fibrinolytic system in health and in disease.